Factors affecting anemia management in hemodialysis patients: a single-center experience

The difficulty maintaining hemoglobin (Hgb) within the targets recommended by KDOQI is widely recognized. While factors responsible for erythropoietin resistance have been widely studied, factors responsible for the marked fluctuations and the inability to maintain Hgb within the target range have only begun to be investigated. This study was a cross-sectional review of anemia management in hemodialysis patients. The purpose was to evaluate factors responsible for Hgb decreases of 0.5 or 1.0 g/dL and to determine the primary factors responsible for Hgb decreases below 11 g/dL. Hgb values and clinical events were extracted from patient management databases between January 1, 2005 and November 30, 2006. Isolated events were defined as events that occurred at least 30 days after any previous event and had Hgb measurements within 2 weeks before and after the event. Increasing hospital length of stay and surgical access intervention were the most common events that resulted in a decrease in Hgb. The most common factor present in patients with Hgb decreases below 11 g/dL was the withholding of recombinant human erythropoietin (rHuEPO) within the preceding 2 months. This was the only explanation for the decrease in Hgb to <11 g/dL in 38.5% of such events. The ability to maintain dialysis patients' Hgb in the target range is complicated by intervening acute events that require hospitalization or surgical access interventions. The withholding of rHuEPO appears to be a major factor in Hgb decreases below 11 g/dL.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis

Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hb<10.0 g/dL with rHuEPO 9000 U/wk or 15 U/kg/wk treatment) into 2 groups as follows: a TJ-48-treated group (TJ-48 group, 7.5 g/d, n=22) and a TJ-48 nontreated (control group, n=20). At the beginning of this study, there was no significant difference between the groups in age, sex, serum creatinine, blood urea nitrogen, serum iron, and ferritin. After 12 weeks of treatment, the Hb level had significantly increased from 8.4 +/- 1.1 to 9.5 +/- 1.3 g/dL (P=0.0272) in the TJ-48 group. C-reactive protein (CRP) had significantly decreased from 1.4 +/- 1.7 to 0.6 +/- 0.8 mg/dL (P=0.0438). There was a significant negative correlation between Hb and CRP in the TJ-48 group (r(2)=0.121, P=0.0066). In contrast, in the control group, Hb and CRP showed no significant changes throughout this study. Nor was there a significant correlation between Hb and CRP in the control group. In conclusion, TJ-48 was effective in improving erythropoietin-resistant anemia in end-stage renal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.     

Tuberculosis in end-stage renal disease patients on hemodialysis

Recent studies have shown that there is an increase in the incidence of mycobacterium tuberculosis (MBT). This is more prevalent among immune compromised patients (those on dialysis) and recipients of organ transplants. Furthermore, extra-pulmonary presentation appears to be more common and difficult to diagnose. We aimed in this study to assess and evaluate the presentation of MBT in a retrospective study conducted among 256 hemodialysis (HD) patients where 18 of them were diagnosed and managed for tuberculosis over a 10-year period between 1990 and 2000. The mean age of the patients was 38 years (21-75 years). The mean interval between the onset of HD and the time of diagnosis was about 24 months (1-120 months). The diagnosis of tuberculosis was made either by isolation of acid-fast bacilli (AFB), the typical caseating granuloma on biopsy, or by recovery of tubercle bacilli from the culture of the biopsy material. Extra-pulmonary tuberculosis was more common (77.8%) than pulmonary tuberculosis (22.2%). The various extra-pulmonary tuberculosis sites noted were cervical lymphadenitis (16.7%), gastrointestinal (16.7%), genitourinary (11.1%), peritonitis (11.1%), pleural effusion (5.6%), pericardial effusion (5.6%), miliary tuberculosis (5.6%), and pyrexia of unknown origin (5.6%). None of the patients with extra-pulmonary tuberculosis had evidence of pulmonary tuberculosis. The atypical presentation with insidious onset was quite common. Anergy to tuberculin skin test was noticed in 56% of cases. All of our patients received modified antituberculosis treatment for 1 year with adequate response, and without undue side effects. We conclude that a high index of suspicion is required especially in the diagnosis of extra-pulmonary tuberculosis, and when there is a high percentage of anergy to tuberculin skin test. Tissue biopsy both for characteristic histology and demonstration of MTB, either by staining or culture, remains the main criteria for the diagnosis of extra-pulmonary tuberculosis.     

Effect of ethnicity on erythropoietin therapy response for hemodialysis patients: A retrospective study

Anemia is a common feature in chronic kidney disease patients due to deficiency of erythropoietin (EPO). Diseased kidneys are unable to produce EPO, which enhances red blood cell production from the bone marrow. Recombinant human EPO in hemodialysis patients was introduced with perfect outcomes as a hormonal substitutive treatment. Some ethnic minority groups have high prevalence of anemia associated with chronic kidney diseases. The aim of this study is to evaluate the differences between African Caribbeans and Caucasians’ EPO therapy response with regard to hemoglobin (Hb), some factors affecting it and some comorbid conditions. A retrospective study for 6 months of 100 patients on hemodialysis was conducted on two ethnic minorities groups; 46 patients were African Caribbean and 54 patients were Caucasian, who received EPO therapy at once or three times weekly dose at the Hanbury Dialysis Unit of Royal London Hospital. There were three types of EPO therapy used: Aranesp, Mircera and Neorecormon. Forty‐six patients were African Caribbean and 54 patients were Caucasian. There were 63.4% of patients treated by Aranesp while 13% were given Mircera; 22.8% of the sample used Neorecorman. It was shown that the chosen comorbid conditions had higher percentage in the African Caribbeans than in Caucasians. Diabetic and/or hypertensive patients are almost double the patient numbers. In addition, sickle cell anemia is only present in African Caribbeans. There were 43.5% of African Caribbeans and 81.1% of Caucasians who met the standards of Hb level. There was no significant difference between African Caribbeans and Caucasians regarding parathyroid hormone, c‐reactive protein, B12, mean corpuscular volume, ferritin, and folate. In this study, there was a significant difference in the Hb levels between African Caribbean and Caucasian groups. Sixty percent of African Caribbeans had mean Hb less than normal levels. However, they received lower EPO dose than Caucasians. As a result, this may affect the whole treatment and therapy which may lead to anemic complications.     

Statin use is associated with lower inflammation and erythropoietin responsiveness index in hemodialysis patients

Patients with end-stage renal disease are prone to inflammation and inflammation is related to erythropoietin-stimulating agent hyporesponsiveness and mortality in this population. Statins have been demonstrated to reduce cardiovascular mortality in selected populations of end-stage renal disease patients. These drugs have pleiotrophic effects such as anti-inflammation. In this retrospective analysis, we determined whether the use of statins improves inflammation and inflammation-related anemia in a cohort of hemodialysis patients. Data were analyzed from Fresenius Medical Care Dialysis Clinics in Turkey between 2005 and 2007. Seventy prevalent hemodialysis patients who were on statins at the start of the study and have been on statins during follow-up (statin users) and 1293 patients who were not on statin at the start of the study and had never been prescribed any lipid-modifying drugs during follow-up (statin nonusers) were included in the study. High-sensitive C-reactive protein levels were significantly decreased in statin users (1.50±1.49 vs. 1.33±1.11 mg/L, P=0.05) compared with nonusers (1.93±3.22 vs. 2.05±2.77 mg/L). Hemoglobin levels and the rate of erythropoietin-stimulating agent users were similar. However, the prescribed erythropoietin-stimulating agent dose (31.6±27.5 vs. 47.3±45.2 U/kg/week, P<0.05) and the erythropoietin response index (2.90±2.73 vs. 4.51±4.48 U/kg/week/Hb, P=0.001) were lower in statin users compared with statin nonusers. On stepwise multiple regression analysis, gender, high-sensitive C-reactive protein, duration of hemodialysis, serum ferritin, and statin use were independent determinants of the erythropoietin responsiveness index. Our results suggest that statin treatment leads to lower inflammation and improves hematopoiesis in hemodialysis patients.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

Disseminated tuberculosis: A neglected entity in immunocompromised hemodialysis patients

End‐stage renal disease is considered a factor predisposing to increased risk of tuberculosis with frequent extrapulmonary localization. Although extrapulmonary tuberculosis has been observed for decades, disseminated tuberculosis, a major cause of morbidity and mortality in immunocompromised hosts, remains rather neglected. We report an unusual case of an immunocompromised patient with a late diagnosis and delayed treatment of genitourinary tuberculosis that subsequently led to the diagnosis of vertebral and miliary tuberculosis (disseminating tuberculosis). Therefore, increased awareness is warranted from physicians dealing with hemodialysis patients in order to avoid delays in diagnosis and treatment initiation.     

Clinical and psychosocial factors predicting health‐related quality of life in hemodialysis patients

Many patients with end‐stage renal disease have significant impairment in health‐related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5‐Dimensional Classification (EQ‐5D) was used to evaluate HRQoL. The mean EQ‐5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ‐5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron‐binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] ?0.008 to ?0.002), anxiety (95% CI ?0.025 to ?0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.     

A comparison of center-based vs. home-based daily hemodialysis for patients with end-stage renal disease

Home hemodialysis has been a therapeutic option for almost 4 decades. The complexity of dialysis equipment has been a factor-limiting adoption of this modality. We performed a feasibility study to demonstrate the safety of center-based vs. home-based daily hemodialysis with the NxStage System One portable hemodialysis device. We also performed a retrospective analysis to determine if clinical effects previously associated with short-daily dialysis were also seen using this novel device. We conducted a prospective, 2-treatment, 2-period, open-label, crossover study of in-center hemodialysis vs. home hemodialysis in 32 patients treated at 6 U.S. centers. The 8-week In-Center Phase (6 days/week) was followed by a 2-week transition period and then followed by the 8-week Home Phase (6 days/week). We retrospectively collected data on hemodialysis treatment parameters immediately preceding the study in a subset of patients. Twenty-six out of 32 patients (81%) successfully completed the study. Successful delivery of at least 90% of prescribed fluid volume (primary endpoint) was achieved in 98.5% of treatments in-center and 97.3% at home. Total effluent volume as a percentage of prescribed volume was between 94% and 100% for all study weeks. The composite rate of intradialytic and interdialytic adverse events per 100 treatments was significantly higher for the In-Center Phase (5.30) compared with the Home Phase (2.10; p=0.007). Compared with the period immediately preceding the study, there were reductions in blood pressure, antihypertensive medications, and interdialytic weight gain. Daily home hemodialysis with a small, easy-to-use hemodialysis device is a viable dialysis option for end-stage renal disease patients capable of self/partner-administered dialysis.     

Management of hypertension in hemodialysis patients

The relationship of hypertension with adverse outcomes is uncertain in the hemodialysis population. If hypertension is an etiologically significant cardiovascular risk factor in hemodialysis patients, the first step would be to assess the level of BP accurately. BP obtained at home over a week and averaged using a validated oscillometric automatic device can prove valuable. To the extent BP lowering influences cardiovascular outcomes, home BP of 150/90 mm Hg would warrant therapy, since it correlates with target organ damage and hypertension diagnosed by ambulatory BP monitoring. To manage hypertension, limiting dietary sodium intake and individualizing dialysate sodium delivery would be first steps. The magnitude of reduction in BP with dietary sodium restriction and the whether dialysate sodium can be safely limited in those who are hypotension-prone is unclear. Antihypertensive drug therapies can effectively reduce BP and are needed by the vast majority of hemodialysis patients. Whether control of hypertension translates into better outcomes is not known, but collective evidence suggests that hypertension should be controlled in hemodialysis patients.     

The deterioration in physical function of hemodialysis patients

Introduction: Physical function in people on hemodialysis deteriorates significantly, however quantification of the rate of deterioration has not been well established. The aim of this study was to examine the rate of deterioration in objective physical function among end‐stage kidney disease patients receiving hemodialysis. Methods: One hundred and ninety‐three participants (mean age 67.5 ±13.2 years, 60.6% males) receiving hemodialysis in Australia. Objective physical function was assessed via the 30‐second sit‐to‐stand and eight‐foot timed up‐and‐go at baseline, 12 and 24 weeks. Findings: We found a decrease in the mean number 30‐second sit‐to‐stands performed from 10.0 (IQR, 4.0 to 13.0); 95% CI (8.0, 11.0) to 8.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 12 weeks to 7.0 (IQR, 0.0 to 11.0); 95% CI (5.5, 9.0) at 24 weeks and a significant overall decreased rate (RR = 0.82; 95% CI, 0.80 to 0.85; P < 0.001). There was a decreased performance in the eight‐foot timed up‐and‐go time from 8.9 seconds (95% CI: 8.1 to 9.7) to 9.0 (95% CI: 8.1 to 9.7) after 12 weeks and further increasing to 9.7 (95% CI: 8.7 to 9.6) seconds after 24 weeks, and overall decreased rate (HR = 0.56; 95% CI, 0.39 to 0.80; P = 0.001) between baseline and week 24. Discussion: Physical function significantly decreases on hemodialysis. Exercise programs to address this physical function decline should be included in hemodialysis treatment regimens.     

Pharmacotherapy considerations in pregnant patients on hemodialysis

Purpose

Successful pregnancy rates on dialysis are increasing with the advent of intensive hemodialysis and advances in medical management.

Summary

Data support the use of intensive hemodialysis in pregnant women with end-stage kidney disease (ESKD). This paper provides an overview of common pharmacotherapeutic changes in management when caring for a pregnant woman receiving intensive hemodialysis. Pregnant patients on peritoneal dialysis were excluded from this analysis due to insufficient data. Topics covered include those related to anemia (iron and erythropoietin stimulating agents), blood pressure agents, monitoring of phosphorus, as well as nutrition and anticoagulation.

Conclusion

When patients on hemodialysis become pregnant, medication adjustments are needed regarding antihypertensives, anemia management, and mineral-bone disease management as many agents require dose adjustment, switching agents due to teratogenicity, or cessation due to fetal complications. There are minimal data in this population; however, successful and healthy infants have been delivered in this patient population with the medication changes discussed.     

Association of bioimpedance spectroscopy‐based volume estimation with postdialysis hypotension in patients receiving hemodialysis

Clinical examination to determine the dry weight of patients on hemodialysis (HD) has been problematic, with studies showing discordance between physician assessment and objective measures of volume status.We studied the association between predialysis bioimpedance spectroscopy (BIS)‐based estimates of fluid overload and postdialysis hypotension in 635 patients in the United States Renal Data System ACTIVE/ADIPOSE (A Cohort study To Investigate the Value of Exercise/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD) study receiving HD in 2009–2011. We recorded predialysis and postdialysis weight and blood pressures over 3 consecutive HD sessions and performed BIS before a single session. Using a previously reported method of estimating normohydration weight, we estimated postdialysis fluid overload (FO_post) in liters. We used logistic regression with extracellular water/total body water (ECW/TBW) or estimated FO_post as the primary predictor and 1 or more postdialysis systolic blood pressures less than 110 mmHg as the dependent variable. Models were adjusted for age, sex, race, ultrafiltration rate per kilogram of body weight, end‐stage renal disease vintage, diabetes mellitus, heart failure, and albumin. Higher ECW/TBW was associated with lower odds of postdialysis hypotension (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15–0.84 per 0.1, P = 0.02). Every liter of FO_post was associated with lower adjusted odds of postdialysis hypotension (OR 0.86, 95% CI 0.79–0.95, P = 0.003). Prospective studies are needed to determine whether this application of BIS could improve current clinical efforts to minimize episodes of postdialysis hypotension without leading to volume overload.     

Correlation between coping style and quality of life among hemodialysis patients from a low‐income area in Brazil

Quality of life (QOL) is an important outcome among end‐stage renal disease patients and can be associated with modifiable behaviors. We analyzed the correlation between coping style and QOL among hemodialysis patients. We studied 166 end‐stage renal disease patients undergoing hemodialysis. They were older than 18 years, under hemodialysis for at least 3 months, and had never received a transplant. Quality of life was assessed by SF‐36 and coping style was scored by the Jalowiec Coping Scale. Emotion‐oriented coping and problem‐oriented coping scores were compared according to sex, comorbidity, and socioeconomic status by the Mann‐Whitney test. Correlations between QOL and 2 coping styles (emotion‐oriented coping and problem‐oriented coping) were adjusted for age, time on dialysis, hemoglobin, creatinine, albumin, calcium–phosphorus product, and Kt/V by backward stepwise linear regression. There was no difference between coping scores according to sex, comorbidity, and socioeconomic status. Emotion‐oriented coping was independently and negatively associated with 4 QOL dimensions: physical functioning, role‐physical, role‐emotional, and mental health. Our results indicate that patients with high emotion‐oriented coping scores should be seen at risk for poor QOL. Patient education in coping skills may be used to change the risk of poor QOL.